title: Cytoplasmic Skp2 expression is increased in human melanoma and correlated with patient survival.
abstract: BACKGROUND
  S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial.
  
  
  METHODS
  To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up.
  
  
  RESULTS
  Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05).
  
  
  CONCLUSIONS
  This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease.
authors.affiliation: Department of Dermatology and Skin Science, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Guangdi
authors.initials: G
authors.lastname: Chen
authors.forename: Yabin
authors.initials: Y
authors.lastname: Cheng
authors.forename: Zhizhong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Magdalena
authors.initials: M
authors.lastname: Martinka
authors.forename: Gang
authors.initials: G
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000378:metabolism; D002648:Child; D015331:Cohort Studies; D003593:Cytoplasm / Q000378:metabolism*; D018450:Disease Progression; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D008875:Middle Aged; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality*; D016019:Survival Analysis; D046888:Tissue Array Analysis; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D044786:S-Phase Kinase-Associated Proteins